Fungicidal activity was observed for RZF versus FLU-S C.
RZF demonstrated rapid killing down to the assay limit of detection by 9 h against both strains of C.
This study demonstrated that RZF anti-Candida and fungicidal activity was retained under in vitro conditions relevant to topical, vaginal application through analysis in MIC assays and evaluation of time-kill kinetics.
Where possible, clinical vaginal isolates were used (CG01, CP01, CP02, and CT02), although RZF MIC values derived herein and in prior MIC studies do not show a significant difference between strains of vaginal versus nonvaginal origin [20, 25].
The test concentrations of RZF and TER of up to 128 [micro]g/ml in MIC and time-kill assays were consistent with the high local concentrations achievable by topical administration, although such drug concentrations presented a challenge and required modification of traditional time-kill methodology.
In time-kill assays, RZF demonstrated fungicidal activity against 11 of 14 Candida strains tested and was near-cidal against the remaining 3 strains.
Whether a similar in vivo efficacy trend with topical RZF would be observed is yet to be determined.
RZF demonstrated the highest levels of killing versus C.
A similar incongruity has been observed for RZF, between the susceptibility and time-kill data presented herein as well as strong efficacy data from rat models of VVC , and the findings of RADIANT, a Phase 2 clinical trial of two topical formulations of RZF in patients with moderate to severe VVC.
Future research may also include characterizing the activity of RZF against Candida biofilms, as recent studies have proposed that biofilms play a role in VVC , although their relevance is not entirely known .
This study demonstrates the retention of anti-Candida activity and fungicidal killing kinetics for RZF under conditions relevant to VVC and at drug concentrations achievable through topical administration.